Certain 2-benzimidazole alkyl carbamates

ABSTRACT

COMPOUNDS CRRESPONDING TO THE FORMULA   1-(R2-CO-),2-(R1-CO-HN-)BENZIMIDAZOLE   WHEREIN R1 IS SELECTED FROM ALKOXY AND ALKOXYALKYL; R2 IS SELECTED FROM ALKYL, ARYL, ALKENYL, THIOALKYL, ALKYLARYL, HALOALKYL, CYCLOALKYL, HALOALKENYL, ALKOXYAKYL, ALKENYLARYL, FURANYL AND CARBOALKOXY. THE COMPOSITIONS DESCRIBED HEREIN ARE USEFUL AS FUNGICIDES AND BIOCIDES.

United States Patent 01 3,658,812 Patented Apr. 25, 1972 hoe ABSTRACT OF THE DISCLOSURE Compounds corresponding to the formula wherein R is selected from alkoxy and alkoxyalkyl; R is selected from alkyl, aryl, alkenyl, thioalkyl, alkylaryl, haloalkyl, cycloalkyl, haloalkenyl, alkoxyakyl, alkenylaryl, furanyl and carboalkoxy. The compositions described herein are useful as fungicides and biocides.

DESCRIPTION OF THE INVENTION The present invention is concerned with a novel group of compounds which can be generally described as 2- benzimidazole carbamates, and their use as pesticides, especially effective against fungi and parasites.

The compounds are represented by the general formula wherein, R is selected from alkoxy and alkoxyalkyl; R is selected from alkyl, aryl, alkenyl, thioalkyl, alkylaryl, haloalkyl, cycloalkyl, haloalkenyl, alkylalkoxy, alkenylaryl, furanyl, and carboalkoxy.

The compounds represented by the above formula can exist in two tautomeric forms as follows:

wherein R and R have been previously defined.

The compounds represented by the above general formulae are manufactured by reacting a 2-benzimidazole alkyl carbamate in an inert solvent with an acid chloride or other like material in the presence of an acid acceptor. The inert solvent can be selected from benzene, chloroform, or the like. The acid acceptor can be selected from triethyamine, pyridine, or the like. In order to illustrate the merits of the present invention, the following examples are provided.

EXAMPLE I 1-n-heptanoyl-2-benzimidazole methyl carbamate A mixture was formed containing 9.5 gm. of 2-benzimidazole methylcarbamate in 100 ml. chloroform. Then 7.4 gm. of heptanoyl chloride was added followed by the dropwise addition of 7 ml. of triethylamine. A solid still remained so another 7.4 gm. of the acid chloride and 7.0 ml. of triethylamine was added portionwise with stirring at 20 to 30 C. After the addition was completed, the mixture was stirred for one hour, washed with 150 ml. water, sodium bicarbonate solution, dried over magnesium sulfate, and evaporated to yield an oil that crystallized from cold n-pentane to yield 12.9 gm. of the solid compound, having a melting point of between 78 and 80 C.

EXAMPLE II Cyclohexylcarbonyl-2-benzimidazole carbamic acid, methyl ester A mixture of 9.5 gm. of 2-benzimidazole methyl carbamate and ml. of chloroform was made. Then, 7.3 gml of cyclohexane carbonyl chloride was added followed bydropwise addition of 7 ml. of triethylamine over a period of 30 minutes at 22 to 30 C. with stirring. The mixture was stirred for an additional 30 minutes and then washed with 5 0 ml. of water and filtered. The chloroform portion was dried over magnesium sulfate and evaporated in a vacuum to yield 9.2 gm. of a solid having a melting point of to C.

EXAMPLE III 1-benzoyl-2-benzimidazole carbamic acid methyl ester A 7 ml. portion of triethylamine was added to a mixture of 9.5 gm. of Z-benzimidazole methylcarbamate, 100 ml. of chloroform and 8.5 ml. of benzoylchloride over a period of 15 minutes, at 20 to 26 C. After one hour, the reaction was still not complete so it was stirred overnight (16 hours). The mixture was diluted with water, filtered, and the chloroform solution was evaporated and dried over magnesium sulfate to give an oil that was washed with ethyl-ether to yield 8.4 gm. of a solid, having a melting point of 140 to 147 C.

Other compounds were prepared in an analogous manner starting with the appropriate starting materials, as outlined above. The following is a table of compounds representative of those embodied by the present invention. Compound numbers have been assigned to them and are used for identification throughout the balance of the specification.

TABLE 1 g a N NHER Com und num r R R2 2 OCH; SCzHs 3 OCH:

4 OCH; CH=CH3 OCH 6 OCH; (fiO--CzH 7 OCH: ()1

8 OCHzCHzOCHa CH OCH cm-( 10 OCH; (3H3 CII;

-CHz-CH-CHz-l(l 31-CH3 11 OCHa CCI=CC12 12 OCH; CHzOCHa 13 OCH; CH3

OHFO

14 OCHg CHzCl 15 OCH; C01 16 OCH; CF: 17 OCH; (011950113 18 OCH;

FUNGICIDE TESTING PROCEDURES (A) iFoliar preventative sprays (1) Bean rust.The chemicals are dissolved in an appropriate solvent and diluted with water containing several drops of Tween-20, a wetting agent. Test concentrations, ranging from 1000 ppm. downward are sprayed to runolf on the primary leaves of pinto beans (Phatreolus vulgarz's L.) After the leaves are dried, they are inoculated with a water suspension of spores of the bean rust fungus (Uromyces phaseoli Arthur) and the plants are placed in an environment of humidity for 24 hours. The plants are then removed from the humidity chamber and held until disease pustules appear on the leaves. Etfectlveness is recorded as percent reduction in number of pustules as compared to untreated inoculated plants.

(2) Bean powdery mildew.Test chemicals are prepared and applied in the same manner as for the bean rust test. After the plants are dry, the leaves are dusted with spores of the powdery mildew fungus (Erysiphe polygoni De Candolle) and the plants are retained in the greenhouse until the fungal growth appears in the leaf surfaces. Effectiveness is recorded as percent of the leaf surface free of fungal growth as compared to untreated inoculated plants.

(B) Foliar eradicative sprays viable, sporulating mycelium as compared to untreated inoculated plants.

(C) Tube systemic test (1) Bean rust-The chemicals are dissolved in an appropriate solvent and diluted with tap water to a series of descending concentrations beginning at 50 p.p.m. Sixty m1. of each concentration are placed in a test tube. A pinto bean plant is placed in each tube and supported with a. piece of cotton so that only the roots and lower stem are in contact with the test solution. Forty-eight hours later the bean leaves are inoculated with a water suspension of spores of the bean rust fungus and placed in an environment with 100% humidity for 24 hours. The plants are then removed from the humidity chamber and maintained in the greenhouse until the disease pustules appear on the leaves. Effectiveness is recorded as the lowest concentra tion, in p.p.m., which will provide 50% reduction in pustule formation as compared to untreated, inoculated plants.

(2) Bean powdery mildew.Test chemicals are prepared and applied in the same manner as for the bean rust systemic test. After two days the leaves are dusted with spores of the powdery mildew fungus and maintained in the greenhouse until mycelial growth appears in the leaf surfaces. Eifectiveness is recorded as the lowest concentration, in ppm, which will provide a 50% reduction in mycelial growth on the leaf surface as compared to untreated, inoculated plants.

BIOCIDE TESTING PROCEDURES Tubes of sterilized nutrient and malt extract broth are prepared. Aliquots of the toxicant, dissolved in an appropriate solvent, are injected through the stopper, into the broth, to provide concentrations ranging from 50 p.p.m. downward. The test organisms consist of two fungi, Aspergillus niger (A.n) van Tieghem and Penicillium italic-um {P.i.) Wehmer, and two bacteria, Escherichia coli (Ea) Migula and Staphylococcus aureus (S.a.) 'Rosenbach. Three drops of a spore suspension of each of the fungi are injected into the tubes of malt broth and three drops of the bacteria are injected into the nutrient broth. One week later the growth of each organism is observed and effectiveness of the chemical is recorded as the lowest concentration in ppm. which provides 50% inhibition of growth as compared to untreated inoculated tubes.

The results of the above tests are set forth in the following table.

TABLE II Eradicative Preventative sprays, p.p.m. sprays, p.p.m.

Tubes stemic In vitro vial (p.p.m.) Rust Mildew Mildew p.p .m.

Compound number Axn. Pi. E.c. 8.0. 1,000 500 100 1,000 500 100 50 25 10 1,000 500 100 Rust Mildew 1 5 0. 03 50 50 100 100 98 100 100 100 100 100 99 5 0 2" 1 0. 05 50 50 100 100 100 100 75 50 50 0 0 0.5 3 5 0.25 50 50 100 98 85 100 100 100 100 100 99 25 25 0 1 0.25 4 0.25 50 50 95 95 50 100 100 100 99 95 so 0 0 0 10 0.25 5 5 0. 05 50 50 100 9a 95 100 100 100 100 100 99 50 50 10 0.50 5 5 0.03 50 50 98 9s 95 100 100 100 100 98 9s 50 25 0 1 0. 05 7 5 0. 03 50 50 100 100 75 100 100 100 100 90 55 50 50 25 5 0.25 8 50 5 50 50 0 50 5 9 5 0. 05 50 50 98 95 75 100 100 25 0 0 1 0.13 5 0. 05 50 50 99 9s 95 100 100 25 25 0 5 (L25 25 0.25 50 10 9s 90 50 100 100 50 25 0 5 0.20 5 0.05 50 50 100 95 25 100 100 25 0 0 1 1113 10 0.13 50 50 100 100 95 100 100 50 25 0 5 0.13 5 0. 05 50 50 75 50 0 99 99 0 0 0 5 0.25 5 0. 05 50 50 99 75 25 95 80 25 0 0 5 m5 5 0. 03 50 50 100 95 80 100 99 25 0 0 5 0.13 5 0.13 50 50 100 100 75 100 100 25 0 0 5 1.0 5 0. 05 50 50 8 95 58 100 0 25 0 5 5 1,

ANTHELMINTIC TESTING METHODS TABLE III P.p.m. Percent eflicac Compound or lethal y (I) Feed testing number to 111155 [N141 N.m. H.7t. so. At. 88 93 4g 0 100 0 0 0 0 Combined observatlons of safety and efficacy of coml 100 0 95 50 5o 50 pounds fed continuously in the diet of mice were made @5 33 g 108 53 133 123 against: Nematospiroides dubius (N.d.), a non-migrating :733 1 3 g 8 g trichostrongyle nematode; Nippostrongysl uslrlnurzs (5117.3, 1 ggg g g 0 8 100 aci 0 ve a a 5 50 a migrating tr1chostrongyle nematode, yp a 750 100 100 100 100 100 (8.0.), a cecal pinworm; Aspzculurzs tetraptera (A.t.), an 1 50 40 0 o 0 4o intestinal pinworm; and Hymenolepis nana (H.n.), an ml 23 g 73 10 1 100 testinal tapeworm. 5% 8 3g 0 8 7 The experimental compounds were welghed out in 500 100 100 u 100 100 specific amounts, premixed with powdered feed 1n a 100 0 0 80 100 500 100 so 50 100 50 mortar and pestle, and blended in a power mixer for to 1 100 70 o N 90 9o min ms 250 50 50 0 100 0 u 500 100 100 50 100 70 Young SWISS Webster mice (12 to 24 g. body weight) 13 1 ggg g8 68 6 9g 63 were obtained from local anim l hubsandl'y Genius and 40 14 500 100 105 100 100 10 housed in pairs in hardware cloth cages. These mice were i 100 put on medicated rations supplied in tared wateproof con- 1 tainers two days prior to inducing infections. Dnnkmg water was supplied ad lib in drip bottles. Feed consump- MgJkg. body weight. tion and weight variations were recorded after the first What is claimed is: week to assess subclimcal tox1c1ty and palatibihty. 1 A composition f matter having the f l After 2.1 days on medicate feed, m1ce were necropsled I and the parasites remaining in the entire small intestine, if R cecum, and colon counted and differentiated. ThlS was n c.m-geg done by compressing the intestinal trace between two 3" x 4" glass plates and examining them under low power magnification. The average number of each species remaining in the medicated groups was compared to average numbers of each species in conrtols. This figure was then subtracted from 100% to yield the percent eflicacy.

(II) Oral dose testing This test was conducted under the same protocol as the feed test, except:

(1) The helminth infections were administered 21 days prior to drug administration.

(2) The experimental compounds were formulated as solutions in Tween 20 and administered orally by stomach tube in mg./kg. dosages.

(3) The sacrifice of the mice was carried out 1 to 3 days following drug administration, and the results are therefore indicative of therapeutic activity.

The results of the above tests are set forth in Table III.

wherein R is methoxy; R is selected from a group consisting of furanyl, styryl and benzyl.

2. The composition of matter as set forth in claim 1, wherein R is styryl.

3. The composition om matter as set forth in claim 1, wherein R is furanyl.

4. The composition of matter as set forth in claim 1, wherein R is benzyl.

References Cited UNITED STATES PATENTS 

